Metallaphotoredox aryl and alkyl radiomethylation for PET ligand discovery.

Positron emission tomography (PET) radioligands (radioactively labelled tracer compounds) are extremely useful for in vivo characterization of central nervous system drug candidates, neurodegenerative diseases and numerous oncology targets1. Both tritium and carbon-11 radioisotopologues are generally necessary for in vitro and in vivo characterization of radioligands2, yet there exist few radiolabelling protocols for the synthesis of either, inhibiting the development of PET radioligands. The synthesis of such radioligands also needs to be very rapid owing to the short half-life of carbon-11. Here we report a versatile and rapid metallaphotoredox-catalysed method for late-stage installation of both tritium and carbon-11 into the desired compounds via methylation of pharmaceutical precursors bearing aryl and alkyl bromides. Methyl groups are among the most prevalent structural elements found in bioactive molecules, and so this synthetic approach simplifies the discovery of radioligands. To demonstrate the breadth of applicability of this technique, we perform rapid synthesis of 20 tritiated and 10 carbon-11-labelled complex pharmaceuticals and PET radioligands, including a one-step radiosynthesis of the clinically used compounds [11C]UCB-J and [11C]PHNO. We further outline the direct utility of this protocol for preclinical PET imaging and its translation to automated radiosynthesis for routine radiotracer production in human clinical imaging. We also demonstrate this protocol for the installation of other diverse and pharmaceutically useful isotopes, including carbon-14, carbon-13 and deuterium.

The Physico-Chemical Properties of Glipizide: New Findings.

The present work is a concrete example of how physico-chemical studies, if performed in depth, are crucial to understand the behavior of pharmaceutical solids and constitute a solid basis for the control of the reproducibility of the industrial batches. In particular, a deep study of the thermal behavior of glipizide, a hypoglycemic drug, was carried out with the aim of clarifying whether the recognition of its polymorphic forms can really be done on the basis of the endothermic peak that the literature studies attribute to the melting of the compound. A number of analytical techniques were used: thermal techniques (DSC, TGA), X-ray powder diffraction (XRPD), FT-IR spectroscopy and scanning electron microscopy (SEM). Great attention was paid to the experimental design and to the interpretation of the combined results obtained by all these techniques. We proved that the attribution of the endothermic peak shown by glipizide to its melting was actually wrong. The DSC peak is no doubt triggered by a decomposition process that involves gas evolution (cyclohexanamine and carbon dioxide) and formation of 5-methyl-N-[2-(4-sulphamoylphenyl) ethyl] pyrazine-2-carboxamide, which remains as decomposition residue. Thermal treatments properly designed and the combined use of DSC with FT-IR and XRPD led to identifying a new polymorphic form of 5-methyl-N-[2-(4-sulphamoylphenyl) ethyl] pyrazine-2-carboxamide, which is obtained by crystallization from the melt. Hence, our results put into evidence that the check of the polymorphic form of glipizide cannot be based on the temperature values of the DSC peak, since such a peak is due to a decomposition process whose Tonset value is strongly affected by the particle size. Kinetic studies of the decomposition process show the high stability of solid glipizide at room temperature.

Three-Dimensional (3D)-Printed Zero-Order Released Platform: a Novel Method of Personalized Dosage Form Design and Manufacturing.

In 2017, there are 451 million people with diabetes worldwide. These figures were expected to increase to 693 million by 2045. The research and development of hypoglycemic drugs has become a top priority. Among them, sulfonylurea hypoglycemic drugs such as glipizide are commonly used in non-insulin-dependent type II diabetes. In order to adapt to the wide range of hypoglycemic drugs and the different individual needs of patients, this topic used glipizide as a model drug, and prepared glipizide preparations with 3D printing technology. The purpose of this study was to investigate the prescription applicability and control-release behavior of structure and explore the application prospects of 3D printing personalized drug delivery formulations. This article aims to establish a production process for personalized preparations based on 3D printing technology. The process is easy to obtain excipients, universal prescriptions, flexible dosages, exclusive customization, and integrated automation. In this paper, the UV method was used to determine the in vitro release and content analysis method of glipizide; the physical and chemical properties of the glipizide were investigated. The established analysis method was inspected and evaluated, and the experimental results met the methodological requirements. Glipizide controlled-release tablets were prepared by the semisolid extrusion (SSE) method using traditional pharmaceutical excipients combined with 3D printing technology. The formulation composition, in vitro release, and printing process parameters of the preparation were investigated, and the final prescription and process parameters (traveling speed 6.0-7.7 mm/s and extruding speed 0.0060-0.0077 mm/s) were selected through comprehensive analysis. The routine analysis results of the preparation showed that the performance of the preparation meets the requirements. In order for 3D printing technology to play a better role in community medicine and telemedicine, this article further explored the universality of the above prescription and determined the scope of application of prescription drugs and dosages. Glipizide, gliclazide, lornoxicam, puerarin, and theophylline were used as model drugs, and the range of drug loading percentage was investigated. The results showed when the solubility of the drug is 9.45 -8.34 mg/mL, and the drug loading is 3-43%; the release behavior is similar.

Computational Drug Repositioning for Chagas Disease Using Protein-Ligand Interaction Profiling.

Chagas disease, caused by Trypanosoma cruzi (T. cruzi), affects nearly eight million people worldwide. There are currently only limited treatment options, which cause several side effects and have drug resistance. Thus, there is a great need for a novel, improved Chagas treatment. Bifunctional enzyme dihydrofolate reductase-thymidylate synthase (DHFR-TS) has emerged as a promising pharmacological target. Moreover, some human dihydrofolate reductase (HsDHFR) inhibitors such as trimetrexate also inhibit T. cruzi DHFR-TS (TcDHFR-TS). These compounds serve as a starting point and a reference in a screening campaign to search for new TcDHFR-TS inhibitors. In this paper, a novel virtual screening approach was developed that combines classical docking with protein-ligand interaction profiling to identify drug repositioning opportunities against T. cruzi infection. In this approach, some food and drug administration (FDA)-approved drugs that were predicted to bind with high affinity to TcDHFR-TS and whose predicted molecular interactions are conserved among known inhibitors were selected. Overall, ten putative TcDHFR-TS inhibitors were identified. These exhibited a similar interaction profile and a higher computed binding affinity, compared to trimetrexate. Nilotinib, glipizide, glyburide and gliquidone were tested on T. cruzi epimastigotes and showed growth inhibitory activity in the micromolar range. Therefore, these compounds could lead to the development of new treatment options for Chagas disease.

Insight into the Dissolution Molecular Mechanism of Ternary Solid Dispersions by Combined Experiments and Molecular Simulations.

With the increase concern of solubilization for insoluble drug, ternary solid dispersion (SD) formulations developed more rapidly than binary systems. However, rational formulation design of ternary systems and their dissolution molecular mechanism were still under development. Current research aimed to develop the effective ternary formulations and investigate their molecular mechanism by integrated experimental and modeling techniques. Glipizide (GLI) was selected as the model drug and PEG was used as the solubilizing polymer, while surfactants (e.g., SDS or Tween80) were the third components. SD samples were prepared at different weight ratio by melting method. In the dissolution tests, the solubilization effect of ternary system with very small amount of surfactant (drug/PEG/surfactant 1/1/0.02) was similar with that of binary systems with high polymer ratios (drug/PEG 1/3 and 1/9). The molecular structure of ternary systems was characterized by differential scanning calorimetry (DSC), infrared absorption spectroscopy (IR), X-ray diffraction (XRD), and scanning electron microscope (SEM). Moreover, molecular dynamic (MD) simulations mimicked the preparation process of SDs, and molecular motion in solvent revealed the dissolution mechanism of SD. As the Gordon-Taylor equation described, the experimental and calculated values of Tg were compared for ternary and binary systems, which confirmed good miscibility of GLI with other components. In summary, ternary SD systems could significantly decrease the usage of polymers than binary system. Molecular mechanism of dissolution for both binary and ternary solid dispersions was revealed by combined experiments and molecular modeling techniques. Our research provides a novel pathway for the further research of ternary solid dispersion formulations.

Synchronized and controlled release of metformin hydrochloride/glipizide from elementary osmotic delivery.

The combination of metformin hydrochloride (MTF) and glipizide (GLZ) is second-line medication for diabetes mellitus type 2 (DMT2). In the present study, elementary osmotic pump ( EOP) tablet is designed to deliver the combination of MTF and GLZ in a sustained and synchronized manner. By analyzing different variables of the formulation, sodium hydrogen carbonate is introduced as pH modifier to improve the release of GLZ, while ethyl cellulose acts as release retardant to reduce the burst release phase of MTF. A two-factor, three-level face-centered central composite design (FCCD) is applied to investigate the impact of different factors on drug release profile. Compared with conventional tablets, the EOP tablet demonstrates a controlled release behavior with relative bioavailability of 99.2% for MTF and 99.3% for GLZ. Data also shows EOP tablet is able to release MTF and GLZ in a synchronized and sustained manner both in vitro and in vivo.

Stable amorphous binary systems of glipizide and atorvastatin powders with enhanced dissolution profiles: formulation and characterization.

The aim of this study was to enhance the dissolution profile of the combination of glipizide and atorvastatin used for simultaneous treatment of hyperglycemia and hyperlipidemia. The strategy to formulate coamorphous glipizide-atorvastatin binary mixture was explored to achieve enhancement in dissolution. The coamorphous glipizide-atorvastatin mixtures (1:1, 1:2 and 2:1) were prepared by cryomilling and characterized with respect to their dissolution profiles, preformulation parameters and physical stability. Amorphization was found to be possible by cryomilling at various tried ratios of the two drugs. The data obtained from glass transition temperatures and from Raman spectroscopy point toward practically no interaction between the two drugs. The dissolution studies revealed the highest enhancement in dissolution profiles of cryomilled coamorphous mixtures containing GPZ:ATV in ratios 1:1 (B-5) and 2:1 (B-7). These two mixtures were, therefore, subjected to studies for the evaluation of precompression parameters in order to find their amenability to satisfactory compression into tablet dosage form. The selected formulation was found to be stable when subjected to accelerated stability testing at 40°. C/75% RH for six months as per ICH guidelines. Based on all these studies, it was concluded that GPZ:ATV (1:1) combination may be able to provide an effective therapy for the comorbidities of hyperglycemia and hyperlipidemia.

Stable Co-crystals of Glipizide with Enhanced Dissolution Profiles: Preparation and Characterization.

Present study deciphers preparation of co-crystals of lipophilic glipizide by using four different acids, oxalic, malonic, stearic, and benzoic acids, in order to achieve enhanced solubility and dissolution along with stability. All co-crystals were prepared by dissolving drug and individual acids in the ratio of 1:0.5 in acetonitrile at 60-70°C for 15 min, followed by cooling at room temperature for 24 h. FT-IR spectroscopy revealed no molecular interaction between acids and drug as the internal structure and their geometric configurations remain unchanged. Differential scanning calorimetry revealed closer melting points of raw glipizide and its co-crystals, which speculates absence of difference in crystallinity as well as intermolecular bonding of the co-crystals and drug. PXRD further revealed that all the co-crystals were having similar crystallinity as that of raw glipizide except glipizide-malonic acid co-crystals. This minor difference in the relative intensities of some of the diffraction peaks could be attributed to the crystal habit or crystal size modification. SEM revealed difference in the crystal morphology for all the co-crystals. Micromeritic, solubility, dissolution, and stability data revealed that among all the prepared co-crystals, glipizide-stearic acid co-crystals were found superior. Hence, it was concluded that glipizide-stearic acid co-crystals could offer an improved drug design strategy to overcome dissolution and bioavailability related challenges associated with lipophilic glipizide.

Controlled release matrix tablets of glipizide: Influence of different grades of ethocel and Co-excipient on drug release.

The aim of the current study was to formulate and evaluate glipizide controlled release matrix tablets by means of different grades of polymer Ethoceland different co-excipients in order to evaluate their effect on drug release profiles during in vitro dissolution studies. Type II diabetes mellitus is usually treated with Glipizide. Glipizide belongs to sulfonylurea group. Gastric disturbance and severe hypoglycemia has been observed after taking glipizide orally. To overcome these problems, controlled release matrices were developed using different grades of ethyl cellulose polymer with a drug-polymer ratio of 1:3by the direct compression method. The effect on drug release of partial replacement of lactose by different co-excipients, HPMC K100M, starch and CMC, were also studied. Diameter, thickness, hardness, friability, weight variations, drug contents of formulations were tested, these properties were within prescribed limits. Co-excipients and polymer containing formulations were compared to the without co-excipients and polymer containing formulations with respect to their release profile. After a 24-hour release study, ethyl cellulose polymer containing formulation exhibited prolonged release for 5-16 hours; however the polymer Ethocel (R) standard FP 7 Premium without co-excipient containing formulation exhibited controlled release for 24 hours. Incompatibility was investigated between drugs, co-excipient DSC and polymer study was performed and any type of interaction was not found. Different kinetic models were used to study the release mechanism. An enhanced release rate was observed in case of excipients containing formulations.

Preparation and in vitro characterization of a non-effervescent floating drug delivery system for poorly soluble drug, glipizide.

The aim of the present study was to formulate a non-effervescent floating drug delivery system of glipizide, a poorly water soluble drug. The solubility of glipizide was initially enhanced using a solid dispersion (SD) strategy with the help of hydrophilic carriers such as poloxamer, cyclodextrin, and povidone. The optimized core material/SD was further formulated into non-effervescent floating tablets (NEFT) by using matrix ballooning inducers, such as crospovidone and release retarding agents including HPMC and PEO. Poloxamer-based solid dispersions prepared by a solvent evaporation technique showed the highest dissolution rate (1 : 10 drug to carrier ratio) compared with all other dispersions. NEFT were evaluated for all physico-chemical properties including in vitro buoyancy, dissolution, and release rate. All of the tablets were found to be within pharmacopoeial limits and all of the formulations exhibited good floating behavior. The formulations (F2 and F3) were optimized based on their 12 h drug retardation with continuous buoyancy. The optimized formulations were characterized using FTIR and DSC and no drug and excipient interaction was found. In-vitro buoyancy and dissolution studies showed that non-effervescent floating drug delivery systems provide a promising method of achieving prolonged gastric retention time and improved bioavailability of glipizide.

Design and evaluation of mucoadhesive beads of glipizide as a controlled release drug delivery system.

The present work aims at the development of a low-cost controlled release system of glipizide beads embedded in pectin to overcome the problem of frequent dosing of drug. The method of preparation has been optimised by experimental design to achieve satisfactory responses with respect to controlling variables. The controlling variables are X1, drug-polymer ratio; X2, surfactant concentration and X3, isooctane-acetone ratio. The most effective combination is X1(1:6), X2(1%), X3(50:50). Various parameters such as mucoadhesivity and swellability of beads, characterisation, dissolution, stability, ex vivo absorption and in vivo (Oral glucose tolerance test in rat) studies were performed with the optimised product. The optimised product was found quiet satisfactory that showed yield of 86.78%, drug entrapment efficiency (DEE) of 87.38% and drug release was extended up to 18 h. The present formulation of glipizide is a promising multiparticulate system of glipizide with significant hypoglycemic effect, and moreover it was prepared rapidly with ease.

[Modification on the interaction of glipizide with bovine serum albumin by molecular spectroscopy].

In the Tris-HCl buffer solution with pH was 7.40, the interaction between glipizide (Gli) and bovine serum albumin (BSA) was investigated by classical fluorescence spectroscopy with the change of protein as investigation object and elastic scattering fluorescence spectrometry with the change of drugs as investigation object at 293 K and 303 K, the conclusions of the two methods were consistent. Results showed that Gli could quench the intrinsic fluorescence of BSA, and the quenching mechanism was a dynamic quenching process. The hydrophobic force played an important role in the conjugation reaction between BSA and Gli, the binding site mainly located in BSA hydrophobic region and the number of binding site (n) in the binary system was approximately to 1. The values of Hill's coefficients were less than 1, which indicated the weak negative cooperativity in BSA-Gli system. The binding constant (Ka) obtained by elastic scattering fluorescence spectrometric was much larger than the one obtained by classical fluorescence spectroscopy, indiciating that it was more accurate and reasonable when using the change of drug's fluorescence as the research object. At last, the scientificalness of the new method based on elastic scattering fluorescence spectrometric was verified by ultraviolet spectroscopy. The research results showed that there existed insufficiency in analysis of the interaction of drug with protein by classical fluorescence spectroscopy with the change of protein as investigation object, and the fluorescence spectrogram only reflected partial information of the interaction between drug and protein, while the interaction between drug and protein could be better expressed by elastic scattering fluorescence spectrometry with the change of drugs as investigation object.

Exploring the mechanism of interaction of glipizide with DNA: Combined in vitro and bioinformatics approach.

DNA, vital for biological processes, encodes hereditary data for protein synthesis, shaping cell structure and function. Since revealing its structure, DNA has become a target for various therapeutically vital molecules, spanning antidiabetic to anticancer drugs. These agents engage with DNA-associated proteins, DNA-RNA hybrids, or bind directly to the DNA helix, triggering diverse downstream effects. These interactions disrupt vital enzymes and proteins essential for maintaining cell structure and function. Analysing drug-DNA interactions has significantly advanced our understanding of drug mechanisms. Glipizide, an antidiabetic drug, is known to cause DNA damage in adipocytes. However, its extract mechanism of DNA interaction is unknown. This study delves into the interaction between glipizide and DNA utilizing various biophysical tools and computational technique to gain insights into the interaction mechanism. Analysis of UV-visible and fluorescence data reveals the formation of complex between DNA and glipizide. The binding affinity of glipizide to DNA was of moderate strength. Examination of thermodynamic parameters at different temperatures suggests that the binding was entropically spontaneous and energetically favourable. Various experiments such as thermal melting assays, viscosity measurement, and dye displacement assays confirmed the minor grove nature of binding of glipizide with DNA. Molecular dynamics studies confirmed the glipizide forms stable complex with DNA when simulated by mimicking the physiological conditions. The binding was mainly favoured by hydrogen bonds and glipizide slightly reduced nucleotide fluctuations of DNA. The study deciphers the mechanism of interaction of glipizide with DNA at molecular levels.

Simultaneous quantification of metformin and glipizide in human plasma by high-performance liquid chromatography-tandem mass spectrometry and its application to a pharmacokinetic study.

A selective, sensitive and rapid high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method was developed and validated to determine metformin and glipizide simultaneously in human plasma using phenacetin as internal standard (IS). After one-step protein precipitation of 200 µL plasma with methanol, metformin, glipizide and IS were separated on a Kromasil Phenyl column (4.6 × 150 mm, 5 µm) at 40°C with an isocratic mobile phase consisting of methanol-10 mmol/L ammonium acetate (75:25, v/v) at a flow rate of 0.35 mL/min. Electrospray ionization source was applied and operated in the positive mode. Multiple reaction monitoring using the precursor → product ion combinations of m/z 130 → m/z 71, m/z 446 → m/z 321 and m/z 180 → m/z 110 were used to quantify metformin, glipizide and IS, respectively. The linear calibration curves were obtained over the concentration ranges 4.10-656 ng/mL for metformin and 2.55-408 ng/mL for glipizide. The relative standard deviation of intra-day and inter-day precision was below 10% and the relative error of accuracy was between -7.0 and 4.6%. The presented HPLC-MS/MS method was proved to be suitable for the pharmacokinetic study of metformin hydrochloride and glipizide tablets in healthy volunteers after oral administration.

[The development of co-amorphous drug systems].

Converting two poorly water-soluble crystalline drugs to co-amorphous drug systems by ball milling, quench-cooling, or cryo-milling method can improve stability of the drug, enhance dissolution rates, and reduce adverse reactions of the single drug. Co-amorphous system has been used to solve problems of co-administration of medicines. Formation and intermolecular interactions of co-amorphous drug systems may be verified by differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD), Raman spectroscopy (RS) and Fourier transform infrared spectroscopy (FT-IR). Stability of co-amorphous drug systems is influenced by their glass transition temperature (Tg) and intermolecular interactions. The theoretical Tg values and the interaction parameter x are calculated by Gordon-Taylor equation and the Flory-Huggins equation, respectively. Thus, co-amorphous drug systems are analyzed theoretically at molecular level. Co-amorphous drug systems provide a new sight for the co-administration of medicines.

[Applicability of a natural swelling matrix as the propellant of osmotic pump tablets].

The purpose of this study is to investigate the applicability of a natural swelling matrix derived from boat-fruited sterculia seed (SMS) as the propellant of osmotic pump tablets. The sugar components, static swelling, water uptake and viscosity of SMS were determined and compared with that of polythylene oxide (WSR-N10 and WSR-303). Both ribavirin and glipizide were used as water-soluble and water-insoluble model drugs. Then, the monolayer osmotic pump tablets of ribavirin and the bilayer osmotic pump tablets of glipizide were prepared using SMS as the osmotically active substance and propellant. SMS was mainly composed of rhamnose, arabinose, xylose and galactose and exhibited relatively high swelling ability. The area of the disintegrated matrix tablet was 20.1 times as that at initial after swelling for 600 s. SMS swelled rapidly and was fully swelled (0.5%) in aqueous solution with relative low viscosity (3.66 +/- 0.03) mPa x s at 25 degrees C. The monolayer osmotic pump tablets of ribavirin and the bilayer osmotic pump tablets of glipizide using SMS as propellant exhibited typical drug release features of osmotic pumps. In conclusion, the swelling matrix derived from boat-fruited sterculia seed, with low viscosity and high swelling, is a potential propellant in the application of osmotic pump tablets.

Hot melt granulation: a facile approach for monolithic osmotic release tablets.

The aim of this work was to develop and evaluate an extended release matrix tablet of glipizide (GP), an oral hypoglycemic agent. Matrices of GP were prepared using microcrystalline cellulose Avicel(™) PH 112, sodium chloride (SC) and polyethylene glycol 6000 (PEG). The content of Kollidon SR (KR), hydroxypropyl methylcellulose K4M premium CR grade (HM) and polyethylene oxide WSR 303 (PO) and/or magnesium hydroxide (MH) was varied in different formulations. All the formulations were processed by hot melt granulation technique. GP release was observed to be influenced by the amount of SC and MH present in the core formulation. The matrix tablets were coated with a solution containing combination of cellulose acetate 398.10 (CA) and PEG. The release of GP was observed to be inversely proportional to the weight of the coating membrane. Matrices containing PO in combination with SC and MH (14.28:8.56) showed significantly higher degree of hydration and swelling that was evident in the surface texture as visualized by scanning electron microscopy (SEM). Results of SEM studies confirmed the presence of pores in the semi-permeable coating membrane from where the GP release would have occurred. The release of GP from this formulation was similar to that of the marketed extended release tablet as judged from similarity factor (f2) analysis, which yielded a value of 74.7. The optimized formulation was found to be stable when tested according to long term and accelerated storage conditions of ICH guidelines upto 3 months.

[Development of glipizide push-pull osmotic pump controlled release tablets by using expert system and artificial neural network].

The purpose of this study is to develop glipizide push-pull osmotic pump (PPOP) tablets by using a formulation design expert system and an artificial neural network (ANN). Firstly, the expert system for the formulation design of osmotic pump of poor water-soluble drug was employed to design the formulation of glipizide PPOP, taking the dissolution test results of Glucotrol XL as the goal. Then glipizide PPOP was prepared according to the designed formulations and the in vitro dissolution was carried out. And in vivo evaluation was carried out between the samples which were similar to Glucotrol XL and the Glucotrol XL in Beagle dogs. The range of the factors of formulation and procedure, which could influence the drug release, was optimized using artificial neural network. Finally, the design space was found. It was found that the target formulation which was similar to Glucotrol XL in dissolution test could be obtained in a short period by using the expert system. The samples which were similar to Glucotrol XL were bio-equivalent to the Glucotrol XL in Beagle dogs. The design space of the key parameter coating weight gain was 9.5%-12.0%. It could be concluded that a well controlled product of glipizide PPOP was developed since the dissolution test standard of our product was more strict than that of Glucotrol XL.

Formulation, Characterization, and Pharmacokinetic Evaluation of Novel Glipizide-phospholipid Nano-complexes with Improved Solubility and Bio-availability.

BACKGROUND: The proposed study was aimed to formulate and evaluate the glipizidephospholipid nano-complex. Since glipizide is a poorly soluble drug, its complexation with phospholipids is an ideal approach to improving solubility. METHODS: To improve the oral potency of glipizide, its phospholipid complex was prepared by employing the solvent evaporation method. The formulations were characterized using DSC, FTIR, PXRD, SEM, TEM, and hot stage microscopy (HSM). Solubility tests of the glipizidephospholipid nano-complex revealed a significant increase in aqueous solubility compared to glipizide's physical combination. The oral bioavailability of the glipizide-phospholipid nanocomplex was measured by using HPLC in Wistar rats' plasma. FTIR and PXRD results revealed no significant interaction between the drug and the phospholipid in the formulation. SEM and TEM studies confirmed the morphology of the formulation assuring the conversion of crystalline form into an amorphous structure. RESULTS: The glipizide-phospholipid nano-complex had a greater peak plasma concentration (5.2 vs. 3.8 g/mL), a larger AUC (26.31 vs. 19.55 µgh/L), and a longer T1/2 (2.1 vs. 4.1 h) than free glipizide, indicating that it improved drug dissolution rate. CONCLUSION: The outcomes suggested that a phospholipid complexation is a potential approach to increasing water-insoluble drugs' oral bioavailability.

Novel microporous resin-based polymer device for sustained glipizide release: Production, characterization and pharmacokinetic study.

The objective of this study was to explore an innovative sustained release technology and design a new microporous resin-based polymer device (RPD) for controlled release of glipizide (GZ). Photocurable resin was applied to prepare the resin layer to control GZ release. The impact of formulation parameters consisting of the type and amount of pore formers and pH modifiers, photocurable curing time as well as the weight of resin layer on GZ release were examined. The GZ-RPD was fabricated applying 24 mg of resin layer with PEG400 (100 % of the resin weight) as pore former and 10 mg of Na2CO3 as pH modifier. Scanning electron microscopy (SEM) demonstrated resin particles presenting a porous structure constituted the resin layer. The GZ-RPD possessed prolonged Tmax and reduced Cmax relative to commercial tablets. The relative bioavailability of the RPDs as well as commercial tablets was 93.65 % since the AUC0-24 h were 6111.05 ± 238.89 ng·h/mL and 6525.09 ± 760.59 ng h/mL, respectively. The release mechanism of the GZ-RPD was discussed. This paper provided an innovative concept to produce controlled GZ release oral formulation fabricated by photocurable resin, which demonstrated both excellent in vitro release and in vivo pharmacokinetics.